Covariation Between Brain Function (MEG) and Structure (DTI) Differentiates Adolescents with Fetal Alcohol Spectrum Disorder from Typically Developing Controls

Abstract

The behavioral, cognitive, and sensory difficulties experienced by individuals exposed to alcohol prenatally currently fail to provide early identification for fetal alcohol spectrum disorder (FASD). Attempting to advance this pursuit through a multivariate analysis, we collected magnetoencephalography (MEG) data during auditory, somatosensory, visual paradigms, DTI, and behavior in adolescents ages 12-21 years (FASD: N = 13; HC: N = 20). We assessed the relationship between brain function (MEG) and structure (fractional anisotropy (FA)) utilizing joint independent component analysis (jICA), and examined how this measure relates to behavior. We identified 5 components that reveal group differences in co-variation between MEG and FA. For example, component 5 (t = 3.162, p = 0.003, Hedges' g = 1.13) contained MEG activity corresponding to all three sensory modalities, most robustly in occipital lobes, and DTI-derived cerebellar FA, underlying the role of the cerebellum in sensory processing. Further, in HCs component 5's loading factor was positively correlated with verbal ability (r = 0.646, p = 0.002), indicating higher covariation was associated with better verbal performance. Interestingly, this relationship is lacking in FASD (r = 0.009, p = 0.979). Also, component 5 loading factor negatively correlated with impulsivity (r = -0.527, p = 0.002), indicating that stronger function-structure associations were associated with individuals with lower impulsivity. These findings suggest that multimodal integration of MEG and FA provides novel associations between structure and function that may help differentiate adolescents with FASD from HC.

Keywords: diffusion tensor imaging (DTI); fractional anisotropy (FA); joint independent component analysis (jICA); magnetoencephalography (MEG); prenatal alcohol exposure (PAE).

Figure 1:. Regional Division of MEG planar gradiometer sensors.

Inserts show Local Field Power of MEG. Calibration bar y-axis is in normalized units.

Figure 2:. jICA Loading Factors:

Values represent group average Loading Factors for each significant component. Error bars: SEM

Figure 3:. MEG time courses.

In the group comparison time courses, the solid line represents HC and dashed line represents FASD. Calibration bar y-axis is in normalized units. Each component timecourse below is described by first the sensory stimulation condition and second by the LFP region where the response was prominent (significantly greater than baseline). Component 5. (A) left auditory, right temporal, (B) right somatosensory, right central, (C) visual, left occipital. (D) visual, left occipital, group comparison. Component 15. (E) left auditory, right temporal. (F) left somatosensory, left central. (G) right somatosensory, right temporal. (H) right somatosensory, right temporal, group comparison. Component 8. (I) right somatosensory, right central. (J) right somatosensory, right central, group comparison. Component 11. (K) right somatosensory, right central. (L) right somatosensory, right central, group comparison. Component 4. (M) visual, left parietal. (N) visual, right occipital. (O) visual, right occipital, group comparison

Figure 4:. FA maps.

Component 5 HC >FASD. (A) Cerebellar white matter tracts. Component 15 HC>FASD. (B) Posterior limb of the left internal capsule. (C) Left superior corona radiata. (D) Right and left hemisphere short range association fibers, anterior portions of the right hemisphere corpus callosum, anterior right thalamic radiation (connecting thalamus to PFC), and the anterior portion of the right corona radiata. Component 8 FASD>HC. (E) Inferior cerebellar peduncle and the cortico spinal tract. Component 11 HC>FASD. (F) Fornix and left inferior fronto-occipital fasciculus. (G) Right superior corona radiata. Component 4 HC>FASD. (H) Left frontal eye field, superior region of the left corona radiata, left superior longitudinal fasciculus, bi-lateral short-range association fibers. (I) Inferior fronto-occipital and inferior longitudinal fasciculus.

Figure 5:

Solid least squares line and solid circle represent HC. Dashed least squares line and ‘x’ represent FASD. Component 5 loading factor, separated by group, correlated with (A) Wechsler Abbreviated Scale of Intelligence - II vocabulary scores and (B) Cambridge Gambling Task impulsivity scores.